These studies are directed to determine mechanisms involved in the cellular and biochemical events which coordinate stimulus-secretion coupling and synthesis of gastrointestinal peptide hormones in in vitro and in vivo experiments to be performed on experimental animals. Detailed studies will be conducted to determine specific events which control the stimulus-secretion coupling and synthesis of the peptide hormones gastrin, somatostatin, and gastric inhibitory peptide. These studies will be conducted for the use of organ culture techniques of antral and proximal small intestinal mucosa. Synthesis of gastrin, somastatin and gastric inhibitory polypeptide will be assessed by the progressive incorporation of tritium labeled immunoacids and to the individual peptide hormone purified by immunoprecipitation techniques, with the individual peptide hormone concentrations being measured by radioimmunoassay. Events in the stimulus-secretion coupling process will be addressed by detailed investigation of the effects of calcium on gastrin synthesis and secretion and the effects of adenosine and guanosine cyclic nucleotides of gastrin synthesis and secretion. A study of intracellular second messengers will also be applied to somatostatin and gastric inhibitory polypeptide secretion and synthesis. First messenger stimulation of specific gastrointestinal endocrine cells will be studied after the effects of cholinergic, adrenergic, biogenic amines and other gastrointestinal hormones upon the secretion and synthesis of gastrin, somatostatin, and gastric inhibitory polypeptide. The interrelationships between circulating and intraluminal concentrations of gastrointestinal hormone and gastric acid secretion will be examined in the intact animal for use of intragastric titration and individual hormone measurements by radioimmunoassay.